Isolation of primitive endoderm, mesoderm, vascular endothelial and trophoblast progenitors from human pluripotent stem cells
- 27 May 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Biotechnology
- Vol. 30 (6), 531-542
- https://doi.org/10.1038/nbt.2239
Abstract
Drukker and colleagues differentiated human embryonic stem (ES) cells for 3 days and screened the cells for labeling by >400 antibodies. They identified cell-surface markers expressed on four classes of early progenitor cell. To identify early populations of committed progenitors derived from human embryonic stem cells (hESCs), we screened self-renewing, BMP4-treated and retinoic acid–treated cultures with >400 antibodies recognizing cell-surface antigens. Sorting of >30 subpopulations followed by transcriptional analysis of developmental genes identified four distinct candidate progenitor groups. Subsets detected in self-renewing cultures, including CXCR4+ cells, expressed primitive endoderm genes. Expression of Cxcr4 in primitive endoderm was confirmed in visceral endoderm of mouse embryos. BMP4-induced progenitors exhibited gene signatures of mesoderm, trophoblast and vascular endothelium, suggesting correspondence to gastrulation-stage primitive streak, chorion and allantois precursors, respectively. Functional studies in vitro and in vivo confirmed that ROR2+ cells produce mesoderm progeny, APA+ cells generate syncytiotrophoblasts and CD87+ cells give rise to vasculature. The same progenitor classes emerged during the differentiation of human induced pluripotent stem cells (hiPSCs). These markers and progenitors provide tools for purifying human tissue-regenerating progenitors and for studying the commitment of pluripotent stem cells to lineage progenitors.Keywords
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